Therapeutically interesting antitumor compounds have been isolated from natural sources. These compounds are often structurally complex, and for this reason systematic chemical studies on the structural and chemical requisites for drug action have been hindered. Microorganisms are known to convert a variety of organic compounds into metabolites which accumulate in fermentations. It is proposed that microbial transformations of naturally occurring antitumor compounds will result in the production of metabolites which will be useful as drugs. Microbial transformations will be developed as a general method for: a) producing quantities of potentially active metabolites of naturally occurring antitumor compounds; b) providing difficult to synthesize drug metabolites which will facilitate drug metabolism studies in animals and man; and c) establishing a working basis for further structure-activity-relationship studies on complex and biologically active compounds from nature. Microorganisms will be used to produce microbial metabolites of acronycine, withaferin-A, camptothecin, vinblastine, and other compounds as well. Microbial metabolites will be determined by chemical and spectral methods, and the metabolites will be examined for antitumor activity. Fermentation parameters which influence both the quantity and number of microbial metabolites will be investigated.